Chlorine dioxide (ClO.sub.2) has been used experimentally in topical applications for many years. It has been disclosed as being applied as a disinfectant on such skin lesions as acne (Alliger, U.S. Pat. No. 4,084,747, 1978), herpes and fungal infections (Kross, U.S. Pat. No. 4,956,184), to disinfect human skin (Kross, U.S. Pat. No. 4,891,216), for application to general and skin infections (Alliger, U.S. Pat. No. 4,330,531), as a skin cleanser (Brown, U.S. Pat. No. 4,737,307) and antiseptic (Bunyan, U.S. Pat. No. 4,035,483).
One of the major problems in using this type of chemically reactive medication is that in certain instances of application onto a wound or skin, the composition may redden and/or irritate the tissue. This is particularly noticeable in a disease such as acne, or on a diabetic ulcer, where the lesion or the area around it may become red and sensitive.
Although chlorine dioxide is not considered toxic and is non-mutagenic (as is chlorine), it is a strong oxidizing agent which may overcome the body's natural reducing capacity while eliminating infection. This undesirable oxidation reaction may be a reason why chlorine dioxide compositions are still not commercially important as skin or wound disinfectants, nor have they ever become approved drugs--a fact particularly surprising since chlorine dioxide medicaments have been shown to kill all bacteria and viruses in about one minute. The speed of kill is faster than formaldehyde and iodine compounds.
Over the past 15 years a number of additives have been tested with chlorine dioxide generating medicaments in an effort to protect the skin and reduce or eliminate irritation while the lesion is being treated. Two of the more obvious putative solutions to the problem involved the addition of petrolatum and lanolin, since by tradition in topical applications, these agents are highly compatible with body tissue and long considered soothing. These two agents, however, provide little or no oxidative protection, and moreover, reduce the speed of bacterial kill. Other common skin emollients and surface active agents such as mineral oil, caster oil and lecithin were tried. These agents, however, provided little beneficial effect. The inclusion of titanium dioxide and soap also had little, or no, protective effect. Another additive, glyceryl monostearate, actually seemed to worsen the irritation.
Because chlorine dioxide is so highly reactive, many compounds are changed chemically on contact with chlorine dioxide or otherwise influence the reactivity of chlorine dioxide. A number of traditional cosmetic and pharmaceutical additives are not practical for inclusion into chlorine dioxide generating formulations including, for example, urea, vitamins A, C, D or E and oil of lavender, because of chemical incompatibility with chlorine dioxide. Some compounds, for example, metallic compounds, carbohydrates and certain wetting agents, alter the smooth, continuous rate of release of the chlorine dioxide gas from the base material, sodium chlorite and its derivative chlorous acid.
After much experimenting, three additives were unexpectedly discovered that were compatible with the strongly reactive chlorine dioxide and reduced the skin irritation of chlorine dioxide without adversely affecting the pharmacological and antimicrobial activity of chlorine dioxide. These agents are allantoin, glycerine and aloe vera. Although these materials are known in the industry as skin moisturizers, it is quite surprising that these agents would exhibit special protective properties, i.e., reduce skin irritation of chlorine dioxide formulations without affecting the pharmacological and antimicrobial activity of chlorine dioxide solutions.
It is particularly surprising that these agents would reduce skin irritation so well, especially in light of the inactivity of related skin protecting compounds. In point of fact, one of ordinary skill would actually expect fat soluble additives such as lanolin, lecithin and related additives to protect the skin better than allantoin, glycerine and aloe vera, if indeed any additives worked at all. In addition to their skin protecting effect, these materials quite unexpectedly enhance the penetration of chlorine dioxide into the skin.
In experimenting with allantoin, glycerine and aloe vera, it was noted that each of these compounds seemed to speed penetration of the chlorine dioxide medication into the skin. It was first thought that this enhanced penetration might have a deleterious effect in topical applications and perhaps even lead to greater irritation of the area of the skin to which the formulation was applied. The gel form of chlorine dioxide medication, in contrast to the liquid form, can be seen to disappear from the surface of the skin or sore very rapidly. While not being limited by way of theory, it is believed that the penetration enhancement exhibited by compositions of the present invention may actually be related to the protective capacity of the additives.